Showing papers by "Michael Horowitz published in 2002"

Gastric emptying in diabetes: clinical significance and treatment.

Abstract: The outcome of recent studies has led to redefinition of concepts relating to the prevalence, pathogenesis and clinical significance of disordered gastric emptying in patients with diabetes mellitus. The use of scintigraphic techniques has established that gastric emptying is abnormally slow in approx. 30-50% of outpatients with long-standing Type 1 or Type 2 diabetes, although the magnitude of this delay is modest in many cases. Upper gastrointestinal symptoms occur frequently and affect quality of life adversely in patients with diabetes, although the relationship between symptoms and the rate of gastric emptying is weak. Acute changes in blood glucose concentration affect both gastric motor function and upper gastrointestinal symptoms. Gastric emptying is slower during hyperglycaemia when compared with euglycaemia and accelerated during hypoglycaemia. The blood glucose concentration may influence the response to prokinetic drugs. Conversely, the rate of gastric emptying is a major determinant of post-prandial glycaemic excursions in healthy subjects, as well as in Type 1 and Type 2 patients. A number of therapies currently in development are designed to improve post-prandial glycaemic control by modulating the rate of delivery of nutrients to the small intestine.

Microvascular decompression in the management of glossopharyngeal neuralgia: analysis of 217 cases.

Abstract: Objective Glossopharyngeal neuralgia (GPN) is a rare condition that often presents with the seemingly benign symptom of deep throat pain. Medical management of this condition has not been very effective, and surgical therapy has ranged from nerve sectioning to microvascular decompression (MVD). We present our experience with more than 200 patients who underwent MVD for treatment of GPN at our institution. Methods We conducted a retrospective review of our database and identified patients who presented for treatment of presumed GPN. When possible, patients were contacted by telephone for collection of follow-up information regarding symptom relief, complications, functional outcomes, and patient satisfaction. Univariate and multivariate analyses were performed to identify predictors of good outcomes after MVD. Subgroup analyses were performed with quartiles of approximately 50 patients each, for assessment of the effects of improvements in techniques and anesthesia during this 20-year period. Results We observed GPN to be more common among female (66.8%) than male (33.2%) patients, with an overall mean patient age of 50.2 years (standard deviation, 14.4 yr). The most common presenting symptoms were throat and ear pain and throat pain alone, and the mean duration of symptoms was 5.7 years (standard deviation, 5.8 yr; range, 1-32 yr). Symptoms appeared almost equally on the left side (54.8%) and the right side (45.2%). The overall immediate success rate exceeded 90%, and long-term patient outcomes and satisfaction were best for the typical GPN group (with pain restricted to the throat and palate). Complication rates decreased across quartiles for all categories evaluated. Conclusion MVD is a safe, effective form of therapy for GPN. It may be most beneficial for patients with typical GPN, especially when symptoms are restricted to deep throat pain only.

The anorexia of ageing.

Abstract: Ageing is associated with a reduction in appetite and food intake, which has been termed the 'anorexia of ageing'. After age 70-75 years average body weight decreases, even in healthy people, disproportionately due to loss of lean tissue. The 'physiological' anorexia and weight loss of ageing predispose to pathological weight loss and malnutrition. Marked weight loss is common in the elderly and a major cause of morbidity and increased mortality. The cause(s) of the anorexia of ageing are largely unknown. We have identified several possibilities. Animal and preliminary human studies indicate that ageing is associated with increased satiety factors and a reduced feeding drive. Endogenous opioids stimulate eating. We administered i.v. infusions of the opioid antagonist naloxone to young and older adults. Overall, the suppression of food intake was not different in the two age groups, but was increased in older women, suggesting reduced stimulation of feeding by endogenous opioids in this group. Plasma concentrations of the satiety hormone cholecystokinin (CCK) increase with ageing. Intravenous CCK-8 infusion produced greater suppression of food intake in older than young subjects (33.5 vs 15.5% P = 0.026), indicating that sensitivity to the satiating effects of CCK is at least maintained and may increase with age. This raises the possibility of using CCK antagonists as stimulants of appetite and food intake in malnourished older people.

The effects of miglitol on glucagon‐like peptide‐1 secretion and appetite sensations in obese type 2 diabetics

Abstract: Background: Previous studies reported that administration of first generation α-glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon-like peptide-1 (GLP-1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP-1 after AGI therapy in diabetics. GLP-1 plays a role to mediate satiety. Any agent that substantially elevates GLP-1 levels may theoretically reduce hunger, increase satiation and limit food intake. Objectives: This study was performed to analyse the effect of miglitol, a more potent second generation AGI with fewer gastrointestinal side-effects, on the regulation of meal-related GLP-1 secretion and on the change of insulin–glucose dynamics as well as the release of gastric inhibitory polypeptide (GIP), another incretin hormone, after stimulation by an ordinary meal in obese type-2-diabetic subjects. Miglitol's subsequent influences on appetite sensations and food intake were also measured. Design: In total, 8 obese type-2-diabetic women were randomized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days (six doses total) in a double-blind fashion. On day 3 of each treatment period (miglitol or placebo), measurements of GLP-1, GIP, insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast. Appetite ratings with visual analogue scales (VASs) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch. The number of tuna sandwiches eaten at lunch was used to measure food consumption. Results: The plasma GLP-1, glucose, insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment. Miglitol effectively enhanced postprandial GLP-1 release and suppressed plasma GIP secretion. The ingestion of a mixed meal induced a remarkable rise in GLP-1 after miglitol as compared with placebo in overweight diabetic subjects. The meal-related rise in GLP-1 after miglitol was significantly greater at all time-points between 30 and 180 min than after the placebo. The postprandial incremental area under the curve for GLP-1 with miglitol treatment was about twofold that with the placebo. The GLP-1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3-h study period. In the miglitol-treated condition, the average caloric intake at lunch during a 30-min eating period was 12% lower (p < 0.05) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP-1 rise after the breakfast meal by greater than 30% from the placebo-treated condition. Correspondingly, the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before the lunch test. Conclusions: Miglitol induced an enhanced and prolonged GLP-1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic-controlled diabetics. The excessive postprandial GLP-1 elevation after miglitol therapy modified feeding behaviour and food intake, and thereby has potential value in regulating appetite and stabilizing body weight in obese type-2-diabetic patients.

Relationships between intestinal calcium absorption, serum vitamin D metabolites and smoking in postmenopausal women.

Abstract: Smoking has been associated with low bone density, fractures and poor intestinal calcium absorption. Calcium absorption is a critical factor in calcium balance in postmenopausal women but the mechanisms causing decreased absorption efficiency in postmenopausal smokers are controversial and poorly defined. We performed a cross-sectional study of 405 postmenopausal women attending a clinic for the management of osteoporosis to compare intestinal calcium absorption efficiency, serum vitamin D metabolites and parathyroid hormone levels in postmenopausal women who had never smoked, who were smokers previously or who were current smokers, to examine the relationships between these variables in smokers. Two hundred and fifty-two of the women had never smoked, 79 had smoked previously and 74 were current smokers. The hourly fractional rate of calcium absorption was similar in non-smokers and those who had previously smoked. Radiocalcium absorption was less in the 74 smokers compared with the 331 non-smokers [0.60 (0.29 SD) vs 0.71 (0.27); p = 0.004], as were serum calcitriol (p<0.001) and parathyroid hormone (PTH) (p<0.01). There was no difference in the relationship between calcium absorption and serum calcitriol between smokers (r = 0.38) and non-smokers (r = 0.28); hence the impaired calcium absorption in the smokers was almost entirely attributable to suppression of the PTH-calcitriol endocrine axis. In postmenopausal women smoking is associated with a reduction in calcium absorption efficiency due to suppression of the PTH-calcitriol axis. This impairment of calcium absorption could lead to accelerated bone loss and limit the usefulness of dietary calcium supplementation.

Postprandial hypotension in response to duodenal glucose delivery in healthy older subjects.

Abstract: Postprandial hypotension occurs frequently in older people and may lead to syncope and falls. Some recent studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate of gastric emptying. The aim of this study was, therefore, to determine whether the fall in blood pressure induced by intraduodenal glucose is influenced by the rate of nutrient delivery into the small intestine, bypassing the effects of gastric emptying. Eight healthy elderly subjects (four male and four female, age 70.3 ± 3.4 years) were studied on two separate days, in double-blind, randomised order. Glucose was infused intraduodenally at a rate of either 1 or 3 kcal min−1, for 60 min, (0–60 min) followed by 0.9 % saline for a further 60 min (60–120 min). Blood pressure and heart rate were recorded at baseline and every 3 min during the study. Blood glucose and plasma insulin were also determined. Only the 3 kcal min−1 infusion caused a significant fall in systolic (P < 0.001) and diastolic (P < 0.0001) blood pressure and an increase in the heart rate (P < 0.0001). The rises in blood glucose (P < 0.01) and plasma insulin (P < 0.05) concentrations were greater during the 3 kcal min−1 infusion. We conclude that in healthy older subjects, the magnitude of the fall in blood pressure and increase in heart rate induced by intraduodenal glucose infusion is dependent on the rate of nutrient delivery into the small intestine. These results may have relevance to the treatment of postprandial hypotension.

Carbohydrate and Satiety

Abstract: This review focuses on what is known about the effects of carbohydrate on food intake, the potential mechanisms mediating these effects, and the impact of different monosaccharides in humans. The inhibition of subsequent food intake associated with ingestion of carbohydrate appears to result primarily from gastrointestinal signals, including those generated by orosensory stimulation, gastric distension, and perhaps most importantly the interaction of nutrients with receptors in the small intestine. The latter is associated with the release of putative satiety hormones, including glucagon-like peptide-1 and amylin, and slowing of both gastric emptying and small intestinal transit (thereby prolonging gastric distension and increasing the time available for nutrient absorption). The effects of carbohydrate on food intake are dependent on the route of administration (i.e., oral, intragastric, or intraduodenal). Changes in blood glucose and insulin concentrations per se probably do not play a major role in the induction of satiety. Studies relating to the comparative effects of different monosaccharides/carbohydrates have yielded inconclusive results, probably in part owing to substantial differences in methodological approaches.

Glycemic, hormone, and appetite responses to monosaccharide ingestion in patients with type 2 diabetes.

Abstract: To investigate the relative effects of fructose and glucose on blood glucose, plasma insulin and incretin (glucagon-like peptide-1 [GLP-1] and gastric inhibitory peptide [GIP]) concentrations, and acute food intake, 10 (6 men, 4 women) patients with diet-controlled type 2 diabetes (diabetic) (44 to 71 years) and 10 age and body mass index (BMI)-matched (6 men, 4 women) nondiabetic, control subjects with varying degrees of glucose tolerance (nondiabetic), were studied on 3 days. In random order, they drank equienergetic preloads of glucose (75 g) (GLUC), fructose (75 g) (FRUCT) or vehicle (300 mL water with noncaloric flavoring [VEH]) 3 hours before an ad libitum buffet lunch. Mean glucose concentrations were lower after FRUCT than GLUC in both type 2 diabetics (FRUCT v GLUC: 7.5 [plusmn] 0.3 v 10.8 [plusmn] 0.4 mmol/L, P [lt ] .001) and nondiabetics (FRUCT v GLUC: 5.9 [plusmn] 0.2 v 7.2 [plusmn] 0.3 mmol/L, P [lt ] .05). Mean insulin concentrations were approximately 50% higher after FRUCT in type 2 diabetics than in nondiabetics (diabetics v nondiabetics: 23.1 [plusmn] 0.7 v 15.1 [plusmn] 1.3 [mu ]U/mL; P [lt ] .0001). Plasma GLP-1 concentrations after fructose were not different between type 2 diabetics and nondiabetics ( P [gt ] .05). Glucose, but not FRUC, increased GIP concentrations, which were not different between type 2 diabetics and nondiabetics ( P [gt ] .05). Food intake was suppressed 14% by GLUC ( P [lt ] .05 v CONT) and 14% by FRUC ( P [lt ] .05 v CONT), with no difference between the amount of food consumed after GLUC and FRUC treatment in either type 2 diabetics or nondiabetics ( P [gt ] .05). We have confirmed that oral fructose ingestion produces a lower postprandial blood glucose response than equienergetic glucose and demonstrated that (1) fructose produces greater increases in plasma insulin concentration in type 2 diabetics than nondiabetics, not apparently due to greater plasma incretin concentrations and (2) fructose and glucose have equivalent short-term satiating efficiency in both type 2 diabetics and nondiabetics. We conclude that on the basis of improved glycemic control, but not satiating efficiency, fructose may be useful as a replacement for glucose in the diet of obese patients with type 2 diabetes.

Bone Density and Bone-Related Biochemical Variables in Normal Men A Longitudinal Study

Abstract: Background. The objective of this study was to determine the pattern of forearm bone loss and its relationship to markers of bone turnover and sex steroids in normal men. This was a longitudinal study over a median interval of 41 months. The study was conducted in Adelaide, Australia. Study participants were 123 healthy male subjects, between the ages of 20 and 83 years. Methods. Fat-corrected forearm bone mineral content (fcBMC), markers of bone formation (alkaline phosphatase, osteocalcin, procollagen type 1 C-terminal extension peptide) and bone resorption (collagen type I cross-linked telopeptide, hydroxyproline/creatinine, pyridinoline/creatinine, and deoxypyridinoline/creatinine), calculated serum bioavailable testosterone, and serum estradiol were measured. Results. The mean time-weighted rate of change in forearm fcBMC was � 0.33% � 0.72 ( SD ) per year. Bone loss commenced after 30 years of age and increased with age ( p � .001), particularly after age 70 years. There was no relationship between the rate of change in fcBMC and either markers of bone turnover or serum sex steroids. Conclusions. In normal men, bone loss increases with age; there does not appear to be any relationship between this loss and either markers of bone turnover or levels of free androgen or estrogen.

Bow hunter's syndrome in the setting of contralateral vertebral artery stenosis: evaluation and treatment options.

Abstract: Study design A case report. Objective To illustrate a rare case of bow hunter's syndrome in a patient with significant contralateral vertebral artery (VA) occlusive disease. Summary of background data Bow hunter's syndrome is an uncommon condition in which the VA is symptomatically occluded during neck rotation. This case is interesting in that the patient had what appeared to be a normal right VA and occluded left VA when the head was in the neutral position. When the head was rotated 45 degrees to the left, the patient's right VA was occluded (bow hunter's finding), and it became apparent that the left VA was not completely occluded (as it appeared in the neutral position angiogram) but rather was 90% stenosed. The complete occlusion appearance in the neutral position was an angiographic phenomenon caused by competitive flow through the open right VA. When the patient rotated his head to the left, he occluded his right VA and had insufficient blood flow through the left VA, thus creating a symptomatic ischemic state. Methods This case was studied using dynamic computed tomography imaging, single-photon emission computed tomography, transcranial Doppler ultrasound, brain stem auditory evoked potentials, and dynamic range-of-motion cerebral angiography. Results The patient demonstrated bow hunter's syndrome as documented on clinical examination and history. Transcranial Doppler studies, dynamic computed tomography scanning, and cerebral/cervical angiography confirmed the diagnosis and revealed an interesting angiographic pattern, which explained the patient's symptoms and findings only when angiographic flow patterns were taken into consideration. Conclusions Bow hunter's syndrome should be suspected when a patient presents with reproducible vertebrobasilar symptoms on rotating the neck. Quantitative documentation using imaging and electroneurophysiologic tests is important when assessing this subjective process. Careful evaluation of the angiographic imagescan often help explain an odd flow pattern and provide the physician with a range of treatment options.

Helicobacter pylori infection is not associated with delayed gastric emptying or upper gastrointestinal symptoms in diabetes mellitus.

Abstract: This study evaluated the relationship between gastric emptying and upper gastrointestinal symptoms with H. pylori status in patients with diabetes mellitus. Sixty-three outpatients (44 type 1, 19 type 2, age 45 +/- 1.5 years) underwent measurements of gastric emptying of a mixed solid and liquid meal, gastrointestinal symptoms (gastric and esophageal), glycemic control (HbA1c), and autonomic nerve function. Anti-H. pylori IgG antibodies were quantified using a validated kit. Gastric emptying of solid and/or liquid was delayed in 47 (75%) patients, and 31 (49%) had autonomic neuropathy. Fifteen (24%) of the patients were H. pylori positive. There were no differences in gastric emptying (solid retention at 100 min: 67.5 +/- 5.7% vs 63.2 +/- 3.6%; P = 0.63, liquid T50: 35.5 +/- 2.9 min vs 42.5 +/- 3.4 min; P = 0.42), upper gastrointestinal symptoms (gastric 3.9 +/- 0.7 vs 4.0 +/- 0.4; P = 0.94 or esophageal 1.7 +/- 0.5 vs 1.3 +/- 0.2; P = 0.42) or HbA1c (8.8 +/- 0.4% vs 8.6 +/- 0.2%; P = 0.89) between H. pylori-positive and -negative patients. We conclude that H. pylori infection is not associated with delayed gastric emptying or upper gastrointestinal symptoms in diabetes.

Temporary balloon occlusion and ethanol injection for preoperative embolization of carotid-body tumor.

Abstract: We report on the preoperative embolization of a carotid-body paraganglioma by temporary balloon occlusion and ethanol injection. Complete devascularization was achieved without complication. Resection after a short postembolization interval required artery sacrifice. Histologic evaluation revealed that the tumor contained diffuse ethanol-induced microemboli. Compared with unembolized and polyvinyl-alcohol-embolized carotid-body paragangliomas, our technique resulted in no greater adverse effects on the tumor-vessel interface. This procedure is an effective and promising method of preoperative embolization of carotid-body tumors and warrants further experience and study. In this article, we also review the literature on carotid-body tumor embolization and ethanol embolization.

Relationship between the Effects of Cisapride on Gastric Emptying and Plasma Glucose Concentrations in Diabetic Gastroparesis

Abstract: Background/Aims: The effect of erythromycin on gastric emptying is attenuated during hyperglycaemia. The aim of this study was to determine in patients with diabetic gastroparesis w

Effects of dose and timing of calcium supplementation on bone resorption in early menopausal women.

Abstract: Bone resorption follows a circadian rhythm that peaks at night, reflecting the circadian rhythm of serum parathyroid hormone. Our previous studies in early postmenopausal women have established that 1000 mg of calcium given at 9 p. m. reduced bone resorption markers overnight, but not during the day. In contrast, 1000 mg given as a divided dose (500 mg doses at 9 a. m. and 9 p. m. each) reduced bone resorption markers during the day, but not during the night. We have now evaluated the effect of 1500 mg of calcium given as a divided dose of 500 mg in the morning and 1000 mg in the evening on bone resorption. We studied 26 healthy women (median age 56 years) whose menopause was less than five years before. On two days, urine was collected from 9 a. m. to 9 p. m. (day collection), and from 9 p. m. to 9 a. m. (night collection); a further fasting (spot) urine sample was obtained at 9 a. m. at the end of the night collection. On the second day, 500 mg of calcium in the carbonate form was taken at 9 a. m. (at the start of the collection) and a further 1000 mg at 9 p. m. (at the start of the second night collection). Calcium supplementation decreased urinary deoxypyridinoline (DPyr/Cr) during the day (p = 0.08) and night (p < 0.05), as well as urinary pyridinoline (Pyr/Cr) both by day (p < 0.05) and night (p < 0.001). There were also decreases in urine hydroxyproline. We conclude that the acute administration of 500 mg of calcium in the morning and 1000 mg in the evening to early postmenopausal women suppresses bone resorption markers during both the day and night.

Misinterpretation of parahippocampal herniation for a posterior fossa tumor: imaging and intraoperative findings.

Abstract: Tumors of the hippocampal and parahippocampal gyrus are not uncommon, nor are lesions of the cerebellopontine and ambient cisterns. Lesions in these areas include astrocytomas, meningiomas, gangliogliomas, hamartomas, neurilemomas, epidermoids, and dermoids. Preoperative imaging is an important tool that can help distinguish lesions, making surgical therapy more targeted and appropriate. The authors report a case of a 41-year-old man with right-sided atypical trigeminal neuralgia and a left ambient cistern abnormality that was radiologically interpreted as a mesial temporal lobe or extramedullary ambient cistern mass lesion. Surgical exploration for biopsy revealed an abnormal posterior fossa anatomy and a parahippocampal herniation into the perimesencephalic cistern. Biopsy confirmed the finding of normal brain.

Antropyloroduodenal, cholecystokinin and feeding responses to pulsatile and non-pulsatile intraduodenal lipid infusion

Abstract: The contribution of the pulsatile nature of gastric emptying to small intestinal feedback mechanisms modulating antropyloroduodenal motility and appetite is unknown. On separate days, eight healthy male volunteers (18–34 years) received randomized, single-blind, intraduodenal (ID) infusions of 10% Intralipid (2 kcal min−1), either continuously [CID], or in a pulsatile manner [PID] (5 s on/15 s off) and 0.9% saline (control) administered continuously, each at a rate of 1.8 mL min−1 for 3 h. During each infusion, subjective ratings of appetite were assessed and antropyloroduodenal pressures recorded with a 16-lumen manometric assembly incorporating a pyloric sleeve sensor. Plasma cholecystokinin was measured from blood collected at regular intervals throughout the infusion. At the end of each infusion the manometric assembly was removed, subjects were offered a buffet meal and the energy and macronutrient content of the meal was measured. Both ID lipid infusions stimulated isolated pyloric pressure waves (IPPWs) (P 0.05, CID vs. PID). Both intraduodenal lipid infusions decreased hunger (P < 0.05), increased fullness (P < 0.05) and reduced energy intake (P < 0.05) when compared with controls; again there was no difference between CID and PID lipid. We conclude that at the infusion rate of ∼ 2 kcal min−1, the acute effects of intraduodenal lipid on antropyloroduodenal pressures, plasma CCK concentration and appetite are not modified by a pulsatile mode of lipid delivery into the duodenum.